1. Field of the Invention
The invention generally relates to the field of heart surgery. More particularly, the invention relates to the use of treated balloons in heart surgeries.
2. Description of the Relevant Art
Although aortic valve surgery is the gold standard, life saving treatment for symptomatic aortic stenosis, some patients do not undergo surgery. According to the 2003 Euro Heart Survey (lung B, et al, Eur Heart J 2003; 24: 1231-43) one third of community patients above the age of 75 with symptomatic severe aortic stenosis do not undergo surgery. The most apparent reason for this is the high mortality of the aortic valve replacement (AVR) in this population. The Medicare data in 2003 found a 8.8% in-hospital mortality of AVR in 145 000 patients aged over 65. There are other data showing average mortality of AVR up to 20% in octogenarians.
The incidence of known and severe aortic stenosis in US population in 2006 was 318,000 cases, of which only 74,000 had undergone AVR (based on Nkomo et al, Lancet 2006). According to other US estimates for 2006, of the 161,107 cases of ECHO diagnosed severe aortic stenosis over a 10-year period only 61,658 undergone AVR (based on Loma Linda data). Given the bad prognosis of severe symptomatic aortic stenosis, there has been an unmet need for another supplementary/alternative therapy.
Recently there has been considerable change in the technical approach to balloon aortic valvuloplasty (BAV) owing to the progress of percutaneous aortic valve implantation retrograde from the femoral artery and advances in the interventional hardware. A decrease in the complication rate of BAV over the past 15 years has been reported and has important implications regarding the morbidity associated with percutaneous aortic valve replacement techniques. In a recent series of 104 BAV procedures there were no procedural deaths and the incidence of total vascular complications was 9%. In-hospital, 1-, 2- and 3-year mortality rates were 6%, 44%, 62% and 71%, respectively. In the 1980's NHLB1 Balloon Valvuloplasty Registry the procedural mortality was 3% and the in-hospital mortality 11%.
BAV has been well demonstrated to moderately increase aortic valve area by an average of 0.3-0.4 cm2 and reduce mean valvular gradient by roughly 50%. This is achieved despite the use of balloon diameters of 18-24 mm, not far smaller from the diameter of the aortic valve ring. Transient valve leaflet and annular stretch undoubtedly contribute to early recoil. The large majority of patients experience immediate symptomatic improvement.
However, the restenosis rates of 42-83% at 5-9 months and consistently >80% at 1 year remain the Achilles heel of the method and is the reason of the dismal long-term event-free and actuarial survival after balloon aortic valvuloplasty that resembles the natural history of untreated aortic stenosis.
It is now recognized that calcific aortic stenosis is a complex cellular process with features of atherosclerosis and biomineralization similar to osteogenesis, which should have specific pathways for targeted inhibition. Similarly, regulated processes may play a role in restenosis following BAV. Although the mechanisms of restenosis are poorly understood, scar formation and heterotopic ossification are believed to play a central role. If specific targeted inhibition of these processes is completely or even partially successful the long-term results of the BAV procedure will improve and it may become an acceptable treatment of aortic valve stenosis in the elderly.
An increasing number of patients are living into the 80s and beyond. Although many of these patients who may have symptomatic stenosis are acceptable candidates for surgical treatment, many are not. Given the uniform desire on behalf of the elderly for improvement in their quality of life, any advance in the BAV procedure that will limit restenosis and improve its long-term results would be welcome in this population.
The first effort to prevent restenosis following BAV was with radiation. The results of the RADAR pilot trial were published in Cathet Cardiovasc Intervent 2006; 68: 183-92. This was a series of 20 patients over 80 years of age with an estimated operative mortality risk above 15%. They underwent prophylactic external beam radiation therapy (EBRT) starting the day following the BAV procedure and for 3 days. A total dose of 1200 cGy and 1500-1800 cGy was administered in the low and high dose groups of patients. Restenosis was defined as over 50% late loss of acute gain in aortic valve area. By 1 year the restenosis rate in the low dose group was 30% and in the high dose group 11%, results impressively better than historical controls.